Virchows Archiv

, Volume 446, Issue 1, pp 10–14

Immunophenotype of lymphocytic infiltration in medullary carcinoma of the breast

  • Hajime Kuroda
  • Jun-ichi Tamaru
  • Goi Sakamoto
  • Kiyoshi Ohnisi
  • Shinji Itoyama
Original Article


Medullary carcinoma (MC) of the breast is characterized by large anaplastic cells and infiltration by benign lymphocytes. Patients with this pattern of breast carcinoma are considered to have a better prognosis than those with other histological subtypes. We reviewed cases of primary breast carcinoma that were surgically resected between 1990 and 2004. Of these, 13 cases of medullary carcinoma of the breast with lymphocyte infiltration were reported. Tests for CD3, CD4, CD8, CD20, CD56, TIA-1, and granzyme B were performed on paraffin sections. We found that the MC contained very few NK cells, as assessed by their reactivity with the CD56 antibodies. However, MC had a significantly greater percentage of CD3, CD8, TIA-1, and granzyme B lymphocytes infiltrating the stroma of the tumor. Furthermore, more CD8-positive than CD4-positive T-cell lymphocytes were present within the tumor cell nests in MC, as opposed to the proportion in usual ductal carcinoma. The infiltrating cytotoxic/suppressor T cells in MC represent host resistance against cancer, and the high grading of the T-cell infiltration could explain, in part, a key mechanism controlling the good prognosis for this type of tumor and solve the pathological paradox of MC.


Medullary carcinoma CD8 CD56 TIA-1 Granzyme B 


  1. 1.
    Arlen M, Flores L, Elguezbal A, Levowitz BS (1976) Nodal response in medullary carcinoma of the breast. Am J Surg 131:263–266CrossRefPubMedGoogle Scholar
  2. 2.
    Ben-Ezra J, Sheibani K (1987) Antigenic phenotype of the lymphocytic component of medullary carcinoma of the breast. Cancer 59:2037–2041PubMedGoogle Scholar
  3. 3.
    Bhan AK, DesMarais CL (1983) Immunohistologic characterization of major histocompatibility antigens and inflammatory cellular infiltrate in human breast cancer. J Natl Cancer Inst 71:507–516PubMedGoogle Scholar
  4. 4.
    Bloom HJG, Richardson WW, Filed JR (1970) Host resistance and survival in carcinoma of the breast a study of 104 cases of medullary carcinoma is a series of 1,411 cases of breast cancer followed for 20 years. BMJ 3:181–187PubMedGoogle Scholar
  5. 5.
    Gaffey MJ, Frierson HF, Mills SE, Boyd JC, Zarbo RI, Simpson JF, Gross LK, Weiss LM (1993) Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance. Mod Pathol 6:721–728PubMedGoogle Scholar
  6. 6.
    Gaudin C, Dietrich PY, Robache S, Guillard M, Escudier B, Lacombe MJ, Kumar A, Triebel F, Caignard A (1995) In vivo local expansion of clonal T cell subpopulations in renal cell carcinoma. Cancer Res 55:685–690PubMedGoogle Scholar
  7. 7.
    Georgiannos SN, Renaut A, Goode AW, Sheaff M (2003) The immunophenotype and activation status of the lymphocytic infiltrate in human breast cancers, the role of the major histocompatibility complex in cell-mediated immune mechanisms, and their association with prognostic indicators. Surgery 134:827–834CrossRefPubMedGoogle Scholar
  8. 8.
    Hudson JM, Castilleja A, Murray JL, Honda T, Kudelka A, Singletary E, Wharton JT, Ioannides CG (1998) Growth and antigen recognition of tumor-infiltrating lymphocytes from human breast cancer. J Interferon Cytokine Res 18:529–536PubMedGoogle Scholar
  9. 9.
    Marrogi AJ, Munshi A, Merogi AJ, Ohadike Y, El-Habashi A, Marrogi OL, Freeman SM (1997) Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma. Int J Cancer 74:492–501CrossRefPubMedGoogle Scholar
  10. 10.
    Moore OS, Foote FW (1949) The relatively favorable prognosis of medullary carcinomas of the breast. Cancer 2:635–642Google Scholar
  11. 11.
    O’Mahony AM, O’Sullivan GC, O’Connell J, Cotter TG, Collins JK (1993) An immune suppressive factor derived from esophageal squamous carcinoma induces apoptosis in normal and transformed cells of lymphoid lineage. J Immunol 151:4847–4856PubMedGoogle Scholar
  12. 12.
    Rapin V, Contesso G, Mouriesse H, Bertin F, Lacombe MJ, Piekarski JD, Travagli JP, Gadenne C, Friedman S (1988) Medullary breast carcinoma: a reevaluation of 95 cases of breast cancer with inflammatory stroma. Cancer 19:2503–2510Google Scholar
  13. 13.
    Reinfuss M, Stelmach A, Mitus J, Rys J, Duda K (1995) Typical medullary carcinoma of the breast: a clinical and pathological analysis of 52 cases. J Surg Oncol 60:89–94PubMedGoogle Scholar
  14. 14.
    Restifo NP, Marincola FM, Kawakami Y, Taubenberger J, Yannelli JR, Rosenberg SA (1996) Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy. J Natl Cancer Inst 88:100–108PubMedGoogle Scholar
  15. 15.
    Ridolfi RL, Rosen PP, Port A, Kinne D, Mike V (1977) Medullary carcinoma of the breast: a clinicopathologic study with 10-year follow up. Cancer 40:1365–1385PubMedGoogle Scholar
  16. 16.
    Shimokawara I, Imamura M, Yamakawa N, Ishii Y, Kikuchi K (1982) Identification of lymphocyte subpopulations in human breast cancer tissue and its significance: an immunoperoxidase study with anti-human T-and B-cell sera. Cancer 49:1456–1464PubMedGoogle Scholar
  17. 17.
    Tanaka H, Hori M, Ohki T (1992) High endothelial venule and immunocomponent cells in typical medullary carcinoma of the breast. Virchows Arch 420:253–261Google Scholar
  18. 18.
    Tamiolakis D, Simopoulos C, Cheva A, Lambropoulou M, Kotini A, Jivannakis T, Papadopoulos N (2002) Immunophenotypic profile of tumor infiltrating lymphocytes in medullary carcinoma of the breast. Eur J Gynaec Oncol 23:433–436Google Scholar
  19. 19.
    Toso JF, Oei C, Oshidari F, Tartaglia J, Paoletti E, Lyerly HK, Talib S, Weinhold KJ (1996) MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation. Cancer Res 56:16–20PubMedGoogle Scholar
  20. 20.
    Wargotz ES, Silverberg SG (1988) Medullary carcinoma of the breast: a clinicopathologic study with appraisal of current diagnostic criteria. Hum Pathol 19:1340–1346PubMedGoogle Scholar
  21. 21.
    Yakirevich E, Izhak OB, Rennert G, Kovacs ZG, Resnick MB (1999) Cytotoxic phenotype of tumor infiltrating lymphocytes in medullary carcinoma of the breast. Mod Pathol 12:1050–1056PubMedGoogle Scholar
  22. 22.
    Yazawa T, Kamma H, Ogata T (1993) Frequent expression of HLA-DR antigen in medullary carcinoma of the breast. A possible reason for its prominent lymphocytic infiltration and favorable prognosis. Appl Immunohistochem 1:289–296Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Hajime Kuroda
    • 1
  • Jun-ichi Tamaru
    • 1
  • Goi Sakamoto
    • 3
  • Kiyoshi Ohnisi
    • 2
  • Shinji Itoyama
    • 1
  1. 1.Department of PathologySaitama Medical Center, Saitama Medical School 1981Kawagoe, SaitamaJapan
  2. 2.Department of SurgerySaitama Medical CenterSaitamaJapan
  3. 3.Department of Breast PathologyCancer Institute and Hospital, Japanese Foundation for Cancer ResearchJapan

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